This project will undertake the radiochemical syntheses and in vivo evaluation in animals of new ligands for the mu, kappa and delta subtypes of the opiate receptor. Targets for synthesis include both agonists and antagonist ligands for these high affinity binding sites of the mammalian brain. Ligands were chosen for radiolabeling with carbon-11 or fluorine-18 on the basis of affinity, lipophilicity, potential routes of metabolism, and selectivity or specificity for opiate receptor subtypes. New radiolabeled compounds will be evaluated in mice, rats and primates for regional specificity of binding, pharmacokinetics, and metabolism. The goal of this Project is to identify suitable radioligands for quantification of opiate receptor subtypes in the living human brain using Positron Emission Tomography (PET), allowing studies of the role of these receptors in drug abuse and dependence, perception and regulation of pain, and psychiatric diseases.